Jacob Juel Christensen

• Holven, Kirsten Bjørklund; Dahl, Tuva Børresdatter; Bålsrud, Pia; Christensen, Jacob Juel; Ottestad, Inger Olaug & Rundblad, Amanda [Show all 15 contributors for this article] (2026). Cetoleic acid rich fish oil increases plasma levels of eicosapentaenoic and docosapentaenoic acids in healthy volunteers: a double-blinded, randomised, controlled trial. British Journal of Nutrition. ISSN 0007-1145. p. 1–28. doi: 10.1017/S0007114526107958. Full text in Research Archive Show summary

  Intake of fish and supplementation with n-3 polyunsaturated fatty acids (PUFA) are associated with reduced incidence of cardiovascular disease (CVD). Cetoleic acid promotes n-3 PUFA generation in salmon and human HepG2 cells, but data in humans are scarce. To explore the effect of cetoleic acid on n-3 PUFA levels, we performed a double-blinded randomised controlled trial in healthy adults (37 females and 12 males) for four weeks. The participants were randomised to consume either capsules with mackerel oil, naturally rich in cetoleic acid, or a control oil, both with a similar concentration of n-3 PUFA. Clinicaltrials.gov (NCT04841044). Supplements with mackerel oil resulted in higher plasma levels of the n-3 PUFAs 20:4n-3 (Eicosatetraenoic acid) and 20:5n-3 (Eicosapentaenoic acid) as compared with those receiving control oil. In addition, those who received the cetoleic-rich capsules had higher levels of 20:4n-3 in the RBC membrane and a decrease in expression of elongation of very long chain fatty acids protein 5 in peripheral blood mononuclear cells. We found no differences in lipid, glucose or C-reactive protein between the two treatment groups, consisting of healthy subjects. Our data suggests that supplementation with cetoleic-rich mackerel oil may result in increased levels of certain n-3 PUFAs. Further studies should include patients with or at risk for metabolic and CVD.

• Jensen, Silje Marie; Holven, Kirsten Bjørklund; Ulven, Stine Marie; Anfinsen, Åslaug Matre; Dierkes, Jutta & Lysne, Vegard [Show all 7 contributors for this article] (2026). Lipoprotein metabolism and inflammation in healthy young subjects – exploring the postprandial and postabsorptive phases following intake of a standardized meal. Atherosclerosis Plus. ISSN 2667-0909. 65. doi: 10.1016/j.athplu.2026.100572. Full text in Research Archive Show summary

  Background and aims: Commonly measured cardiometabolic biomarkers have not been systematically characterized across the long-term continuum of the postprandial and postabsorptive phases. The aim of the present study was to evaluate how the exact time since last meal impacts test results for lipoprotein particles and inflammatory biomarkers. Methods: We used data from a trial where 34 normal-weighted males and females aged 20-30 y were included. Subjects fasted 12 h, had blood sampled at baseline, then consumed a standardized, habitual breakfast meal, and had blood sampled 13 more times over the next 24 h. NMR metabolomics was used to quantify lipoprotein subclasses and various biomarkers, and ELISA to analyze VCAM-1, ICAM-1, E-selectin, and IL-6. We characterized the postprandial and postabsorptive responses using visualizations and non-linear mixed effects models. Results: Six VLDL subclasses increased by 11-429% within 2-4 h postprandially before returning to baseline levels, followed by another increase 8-10 h after intake of the breakfast meal. IDL and three LDL subclasses increased around 10-12% over 24 h. Four HDL subclasses showed an inverse association with VLDL subclasses, reaching their lowest levels about 1 h after the meal and peaking after 8-10 h with a 5-15% increase from baseline. Participants had an average increase of 325% in IL-6 10 h after breakfast, while other inflammatory biomarkers showed little change over time. For most biomarkers, males generally exhibited higher baseline concentrations compared to females, however the responses over time remained similar. Conclusions: Baseline levels and time of return to baseline varied between individuals, with some sex-specific differences in responses. TG-rich lipoproteins and VLDL increased postprandially and normalized by 12-24 h, whereas IDL and LDL showed minor early changes but increased by 24 h. IL-6 increased markedly during the first 10 h and returned to baseline by 12-24 h, while other inflammatory markers changed little.

• Holven, Kirsten Bjørklund; Raal, Frederick J.; Watts, Gerald F.; Christensen, Jacob Juel & Lennep, Jeanine Roeters van (2026). Challenges in the care of woman with familial hypercholesterolaemia during the reproductive period – current evidence and practical guidance. Atherosclerosis. ISSN 0021-9150. 415. doi: 10.1016/j.atherosclerosis.2026.120679. Full text in Research Archive
• Bålsrud, Pia; Ulven, Stine Marie; Hjartåker, Anette; Ottestad, Inger Olaug; Retterstøl, Kjetil & Schwab, Ursula [Show all 9 contributors for this article] (2026). Association between dietary protein intake and frailty index among home-dwelling older adults; an 8-year follow-up study. The Journal of Nutrition, Health & Aging. ISSN 1279-7707. 30(6). doi: 10.1016/j.jnha.2026.100850. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Retterstøl, Kjetil & Narverud, Ingunn [Show all 10 contributors for this article] (2025). LDL cholesterol burden in elderly patients with familial hypercholesterolemia: Insights from real-world data. American Journal of Preventive Cardiology. 22. doi: 10.1016/j.ajpc.2025.100986. Full text in Research Archive Show summary

  Background and aims Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary heart disease (CHD). While current LDL-C levels usually guides therapy, the cumulative exposure to LDL-C (the LDL-C burden) is suggested to offer a more precise estimate of cardiovascular risk in people with FH. Therefore, using real-world data, this study aimed to estimate the LDL-C burden at different ages in elderly FH patients with and without CHD, and to assess the LDL-C burden at CHD onset. Methods Data was retrospectively collected from the medical records of elderly (>60 years) FH patients at the Lipid Clinic in Oslo. The LDL-C burden (mM-years) was estimated based on repeated LDL-C measurements and information on lipid-lowering medication. Time-weighted average (TWA) LDL-C was calculated as LDL-C burden divided by years. Results We included 112 FH patients, of which 55 (49 %) had experienced at least one CHD-event, and 58 (52 %) were females. Median age at first and last visit were 50 years and 68 years, respectively, with a median of 9 (range; 2–14) available LDL-C measurements. Subjects with CHD had higher LDL-C burden at all ages tested (45, 50 and 60 years) compared with the non-CHD group (p < 0.01, also after adjusting for sex), and had higher TWA LDL-C before treatment at the Lipid Clinic (p = 0.004), but not during follow-up (p = 0.6). There were no sex differences in LDL-C burden at all ages tested, also after adjusting for CHD (p > 0.1). However, women had higher TWA LDL-C during follow-up at the Lipid Clinic (p = 0.01). Median LDL-C burden at CHD onset was 352 mM-years; numerically lower in women than in men (320 vs. 357 mM-years, respectively. p = 0.1). Conclusion Elderly FH patients with CHD had higher estimated LDL-C burden compared with FH patients without CHD, due to higher burden prior to treatment, highlighting the importance of early detection and treatment.

• Nilsen, Christoffer Baustad & Christensen, Jacob J. (2025). Nytt fra internasjonal forskning: Koronar aterosklerose hos metabolsk friske med høyt LDL-C – innsikt fra KETO-CTA-studien. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 23(2), p. 114–121. doi: 10.18261/ntfe.23.2.9. Full text in Research Archive Show summary

  Enkelte som følger et ketogent kosthold opplever dramatisk økning i LDL-kolesterolet tross ellers god metabolsk helse, såkalte Lean Mass Hyper-Responders (LMHR). Bekymringen har vært knyttet til om denne LDL-kolesterolstigningen øker risikoen for hjerte- og karsykdom ved å føre til mer aterosklerose. I denne artikkelen tar vi for oss KETO-CTA-studien som hadde som primærutfall å undersøke endringer i såkalt ikke-kalsifisert koronart plakkvolum hos 100 personer definert som LMHR. Resultatene indikerte en median økning i plakkvolum på 18,8 mm³ over ett år, en økning betydelig større enn forventet, og som antyder rask plakkprogresjon i LMHR-kohorten, sammenlignet med andre grupper. Vi oppsummerer og diskuterer studien, og tar for oss etiske spørsmål om rapportering av primærutfallet, og hvordan forskningen kommuniseres i sosiale medier, samt den hyppig utfordrede hypotesen om at høyt LDL-C er ufarlig ved ellers god risikoprofil.

• Narum, Marte; Christensen, Jacob J.; Holven, Kirsten Bjørklund; Berg, Tore Julsrud & Sveen, Kari Anne (2025). Low LDL particle levels associate with coronary arteries free from atherosclerosis in long-term type 1 diabetes: the Dialong study. Cardiovascular Diabetology. 24. doi: 10.1186/s12933-025-02844-z. Full text in Research Archive Show summary

  Background The risk of developing coronary artery disease (CAD) is increased in type 1 diabetes, due to accelerated atherosclerosis. The molecular mechanisms are yet to be unraveled, but potential functional and quantitative abnormalities in lipoproteins are suggested to be involved. Some individuals have coronary arteries free from atherosclerosis even after living with type 1 diabetes for many decades. We therefore aimed to investigate the associations between a set of lipoproteins and metabolites and the presence of coronary arteries free from atherosclerosis in individuals with long-term type 1 diabetes. Methods Cross-sectional, controlled study of 102 participants with type 1 diabetes and 61 control subjects. We used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify circulating lipids and metabolites in serum. In participants without previously established coronary heart disease (CHD) we performed computed tomography coronary angiography (CTCA). Results In the diabetes group, mean age was 62 (7) [mean (standard deviation, SD)] year and diabetes duration 50.6 (4.9) years. Lower particle concentration of all LDL subclass particles associated significantly with higher odds of having coronary arteries free from atherosclerosis (p < 0.05). Low particle concentration of all LDL subclasses also associated significantly with normal Coronary Artery Calcium (CAC) score (p < 0.05 for all), after adjustment for age, sex, BMI, eGFR and statin treatment. The whole diabetes group, independent of presence of CAD, had significantly lower particle concentration of IDL and all LDL and VLDL subclass particles compared to the control group (p < 0.05 for all). Conclusions In this cohort of long-term survivors of type 1 diabetes, lower levels of all types of LDL particles associated significantly with higher odds of having coronary arteries free from atherosclerosis, after adjustment for statin treatment. These results emphasize the importance of early treatment start and lipid management in the development of CAD in type 1 diabetes and suggest a subgroup of long-term survivors of type 1 diabetes to may hold environmental or genetic protective beneficial traits, independent of statin use. More research on the role of lipoproteins in the development of atherosclerosis in patients with type 1 diabetes is needed.

• Arnesen, Erik Kristoffer; Christensen, Jacob J.; Laake, Ida; Carlsen, Monica Hauger; Veierød, Marit Bragelien & Retterstøl, Kjetil (2025). Low-fat and whole milk consumption in relation to cardiovascular disease–related and all-cause mortality: a prospective cohort study in 3 Norwegian counties. American Journal of Clinical Nutrition. ISSN 0002-9165. 122(4), p. 1075–1085. doi: 10.1016/j.ajcnut.2025.07.035. Full text in Research Archive Show summary

  Background The impact of milk consumption on cardiovascular disease (CVD) risk or mortality is unclear, and specific comparisons between types of milk are scarce. Objectives We aimed to investigate the associations between milk consumption, measured in a large Norwegian cohort in 3 counties during 1974–1988, and CVD–related mortality and all-cause mortality and to compare the associations between whole (full-fat) and low-fat milk. Methods This population-based, prospective cohort study included adults invited to repeated health screenings in the Norwegian Counties Study (>80% attendance). Dietary intake was assessed from food frequency questionnaires at each screening in 1974–1988. Cox regression analysis was used to estimate hazard ratios (HRs) with 95% CIs for the associations between milk intake (assessed as cumulative mean intake from repeated questionnaires) and risk of death from all CVD, ischemic heart disease (IHD), acute myocardial infarction (AMI), and all causes. Results Among 73,860 participants included in this study (mean age: 41.2 years at baseline; 49% females), 26,393 deaths occurred (8590 from CVD, 4372 from IHD, and 3047 from AMI) during a median follow-up of 33 y. Comparing the highest with the lowest quintile of overall milk intake, the HR was 1.12 (95% CI: 1.03, 1.21) for CVD-related mortality and 1.22 (95% CI: 1.16, 1.28) for all-cause mortality. For whole milk, high compared with no intake was positively associated with CVD (HR: 1.07; 95% CI: 0.99, 1.16), IHD (HR: 1.13; 95% CI: 1.01, 1.27), and all-cause mortality (HR: 1.15; 95% CI: 1.10, 1.21). Compared with whole milk, low-fat milk intake was associated with lower CVD-related, IHD-related, AMI-related, and all-cause mortality. The associations were attenuated in analyses considering only baseline intakes. Conclusions In this cohort with high milk consumption, whole milk is associated with higher CVD and all-cause mortality, whereas low-fat milk is not. Low-fat milk may be associated with lower risks than whole milk.

• Christensen, Jacob J; Holven, Kirsten Bjørklund; Bogsrud, Martin Prøven; Retterstøl, Kjetil; Lennep, Jeanine E Roeters van & Michelsen, Trond Melbye [Show all 8 contributors for this article] (2025). Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study. European Heart Journal. ISSN 0195-668X. 47(3), p. 318–327. doi: 10.1093/eurheartj/ehaf592. Full text in Research Archive Show summary

  Background and Aims Statins and other lipid-modifying agents (LMAs) have traditionally been contraindicated during pregnancy due to concerns about harmful fetal effects; however, the risks associated with exposure to statins and other LMAs in human pregnancies remain unclear. Therefore, this study aimed to examine the associations between statin and LMA exposure in pregnancy and congenital malformations in offspring, while updating a 2022 meta-analysis with the results from the present study. Methods National registry data were linked for all pregnant women in Norway in 2005–18. Associations between first-trimester statin prescription fills and congenital malformations were estimated with mixed-effects logistic regression, adjusting for age, parity, pre-pregnancy folate use, smoking in early pregnancy, comorbidity, and co-medication. Meta-analyses were performed with the generic inverse–variance method and random-effects model. Results Congenital malformations occurred among 34 755 out of 803 830 (4.3%) statin non-exposed pregnancies, 74 out of 1255 (5.9%) statin-discontinuer pregnancies, and 19 out of 283 (6.7%) statin-exposed pregnancies. Adjusted odds ratios (ORs) for exposed vs non-exposed pregnancies were 1.30 [95% confidence interval (CI) .81–2.09] for any, 1.15 (.61–2.19) for major, and 1.47 (.75–2.89) for minor malformations. In analyses of exposed vs discontinuer pregnancies, there were no associations between statin exposure and any (adjusted OR 1.01, 95% CI .59–1.72), major (1.08, .52–2.25), or minor malformations (.94, .44–2.00). Results were similar across sensitivity analyses. There was also no association between any LMA exposure and heart malformations (adjusted OR 1.22, 95% CI .50–3.01). The updated meta-analysis suggested no increased risk of major (adjusted OR 1.06, 95% CI .86–1.31) or heart malformations (1.24, 95% CI .94–1.64). Conclusions In this large, nationwide study and updated meta-analysis, no significant association was observed between first-trimester exposure to statins or other LMAs and congenital malformations. Although limited power may have prevented detection of weak but clinically relevant associations, the findings do not support a strong or independent association between statin exposure in pregnancy and congenital malformations.

• Svendsen, Karianne; Christensen, Jacob J.; Igland, Jannicke; Krogh, Henriette Walaas; Mundal, Liv Jorunn & Jacobs, David R. [Show all 9 contributors for this article] (2025). Risk of adverse pregnancy outcomes and impact of statin use in pregnant women with familial hypercholesterolemia. Atherosclerosis. ISSN 0021-9150. 408, p. 1–8. doi: 10.1016/j.atherosclerosis.2025.120442. Full text in Research Archive Show summary

  Background and aims Sparse data exist on the risk of adverse pregnancy outcomes in women with familial hypercholesterolemia (FH). We investigated associations between FH and adverse pregnancy outcomes, and between statin exposure in pregnancy and adverse pregnancy outcomes among women with FH. Methods We studied 3869 pregnancies among 1869 women with genetically-proven FH and 68225 pregnancies among 33661 women from the general population. Data on adverse pregnancy outcomes were obtained during 1967–2018 from the Medical Birth Registry of Norway. Data on pharmacy-dispensed statins were obtained from the Norwegian prescription database (2004–2018) in 1051 women with FH. Associations were presented as odds ratio (OR) with 95 % CI from logistic regression adjusted for mother's age, parity, and offspring's birth year. Results Women with FH had a higher risk of preeclampsia (OR 1.21 [1.00–1.46]), but lower risk for gestational diabetes (OR 0.58 [0.36–0.92]) and intrapartum hemorrhage during delivery (OR 0.81 [0.71–0.92]) compared to controls. No excess risk of adverse pregnancy outcomes in offspring was observed for FH. Among women with FH, statin exposure (mainly in the first trimester) may be associated with higher risk of low birth weight in offspring born at term (OR 2.42 [0.51, 11.45]). Conclusions Women with FH had lower risk of gestational diabetes and intrapartum hemorrhage, but a higher risk of preeclampsia compared to controls. No adverse birth outcomes were observed for offspring of mothers with FH, but the association between statin exposure in pregnant women with FH and low birth weight in offspring warrants further study.

• Parnell, Laurence D.; Lai, Chao-Qiang; Holzapfel, Christina; Christensen, Jacob J. & Ordovás, José M (2025). CC Genotype at TCF7L2 Diabetes Risk Locus rs7903146 Directs a Coordinated Fatty Acid Response to a Mediterranean Diet Intervention: A Randomized Controlled Trial. Lifestyle Genomics. ISSN 2504-3161. 18(1), p. 36–51. doi: 10.1159/000542468. Full text in Research Archive Show summary

  Introduction: Previous studies identified genetic links between the TCF7L2 C/T variant rs7903146, type 2 diabetes (T2D), and obesity. We wished to deepen our understanding of how specific diets interact with this variant to affect blood metabolites, an aspect not previously investigated. Hence, we conducted a controlled study where individuals with different genotypes followed a Mediterranean (Med) or low-fat (LF) diet for 1 week. Methods: Participants were recruited from the Boston, MA (USA) area. Anthropometric and clinical measures were taken. Genotypes at rs7903146 were ascertained, with homozygous carriers of the more common and protective CC or risk TT genotype invited to participate. Participants followed both diets (LF or Med) for 1 week with ∼10 days’ washout between diets. Blood samples taken at the beginning and end of each diet period underwent metabolomics analysis using nuclear magnetic resonance spectroscopy. We evaluated how the diet affected different metabolites based on genetic profile. Results: The cohort of 35 persons was 43% female, aged 18–70 y, with BMI between 26.4 and 33.9 kg/m2. Focusing on fatty acids (FAs) and other lipid metabolic factors (n = 23), we observed a greater number and stronger correlations among these factors in the CC genotype-Med diet group than in the other three genotype-diet combinations. An aggregate of 11 factors, each negatively correlating with delta-saturated fatty acids (SFA), showed a significant genotype-Med diet interaction on delta-SFA in CC individuals on the Med diet (p = 0.0046). A similar genotype-Med diet interaction was observed for delta-monounsaturated fatty acids (p = 0.0078). These interactions were not statistically significant at the end of the LF intervention. Conclusion: Our findings suggest that the Med diet has a stronger influence on regulating lipid factors in individuals with the CC genotype at the TCF7L2 variant rs7903146. This diet-genotype interaction may have significant implications for understanding the inter-individual variation of metabolic response on specific dietary regimens.

• Christensen, Jacob J. (2024). Ultraprosessert mat: en oppdatering. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 22(4), p. 224–228. doi: 10.18261/ntfe.22.4.8. Full text in Research Archive
• Jeevanathan, Janeni; Blom, Sigrid Marie; Olsen, Thomas; Holven, Kirsten Bjørklund; Arnesen, Erik Kristoffer & Trydal, Torleif [Show all 11 contributors for this article] (2024). Real-world impact of transitioning from one lipoprotein(a) assay to another in a clinical setting. American Journal of Preventive Cardiology. 19. doi: 10.1016/j.ajpc.2024.100726. Full text in Research Archive Show summary

  Background and aims: Different lipoprotein(a) [Lp(a)] assays may affect risk stratification of individuals and thus clinical decision-making. We aimed to investigate how transitioning between Lp(a) assays at a large central laboratory affected the proportion of individuals with Lp(a) result above clinical thresholds. Methods: We studied nationwide clinical laboratory data including 185,493 unique individuals (47.7 % women) aged 18-50 years with 272,463 Lp(a) measurements using Roche (2000-2009) and Siemens Lp(a) assay (2009-2019). Results: While the majority of individuals (66-75 %) had low levels of Lp(a) (<30 mg/dL) independent of the assay used, the Roche assay detected 20 % more individuals with Lp(a) >50 mg/dL, 40 % more individuals with Lp(a) >100 mg/dL and 80 % more individuals with Lp(a) >180 mg/dL than the currently used Siemens assay, likely due to calibration differences. Conclusion: Transitioning from one Lp(a) immunoassay to another had significant impact on Lp(a) results, particularly in individuals approaching clinically relevant Lp(a) thresholds.

• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob Juel; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2024). Gene expression profiling in elderly patients with familial hypercholesterolemia with and without coronary heart disease. Atherosclerosis. ISSN 0021-9150. 392. doi: 10.1016/j.atherosclerosis.2024.117507. Full text in Research Archive Show summary

  Background and aims Elderly familial hypercholesterolemia (FH) patients are at high risk of coronary heart disease (CHD) due to high cholesterol burden and late onset of effective cholesterol-lowering therapies. A subset of these individuals remains free from any CHD event, indicating the potential presence of protective factors. Identifying possible cardioprotective gene expression profiles could contribute to our understanding of CHD prevention and future preventive treatment. Therefore, this study aimed to investigate gene expression profiles in elderly event-free FH patients. Methods Expression of 773 genes was analysed using the Nanostring Metabolic Pathways Panel, in peripheral blood mononuclear cells (PBMCs) from FH patients ≥65 years without CHD (FH event-free, n = 44) and with CHD (FH CHD, n = 39), and from healthy controls ≥70 years (n = 39). Results None of the genes were differentially expressed between FH patients with and without CHD after adjusting for multiple testing. However, at nominal p < 0.05, we found 36 (5%) differentially expressed genes (DEGs) between the two FH groups, mainly related to lipid metabolism (e.g. higher expression of ABCA1 and ABCG1 in FH event-free) and immune responses (e.g. lower expression of STAT1 and STAT3 in FH event-free). When comparing FH patients to controls, the event-free group had fewer DEGs than the CHD group; 147 (19%) and 219 (28%) DEGs, respectively. Conclusions Elderly event-free FH patients displayed a different PBMC gene expression profile compared to FH patients with CHD. Differences in gene expression compared to healthy controls were more pronounced in the CHD group, indicating a less atherogenic gene expression profile in event-free individuals. Overall, identification of cardioprotective factors could lead to future therapeutic targets.

• Anfinsen, Åslaug Matre; Myklebust, Vilde Haugen; Johannesen, Christina Osland; Christensen, Jacob J.; Laupsa-Borge, Johnny & Dierkes, Jutta [Show all 10 contributors for this article] (2024). Serum concentrations of lipids, ketones and acylcarnitines during the postprandial and fasting state: the Postprandial Metabolism (PoMet) study in healthy young adults. British Journal of Nutrition. ISSN 0007-1145. 132(7), p. 851–861. doi: 10.1017/S0007114524001934. Full text in Research Archive Show summary

  To improve the interpretation and utilisation of blood lipids, ketones and acylcarnitine concentrations as biomarkers in clinical assessments, more information is needed on their dynamic alterations in response to dietary intake and fasting. The aim of this intervention study was to characterise the changes in serum lipid, ketone and acylcarnitine concentrations 24 h after a standardised breakfast meal. Thirty-four healthy subjects (eighteen males and sixteen females) aged 20–30 years were served a breakfast meal (∼500 kcal, 36 E% fat, 46 E% carbohydrates, 16 E% protein, 2E% fibre), after which they consumed only water for 24 h. Blood samples were drawn before and at thirteen standardised timepoints after the meal. Metabolite concentrations were plotted as a function of time since the completion of the breakfast meal. Results demonstrated that concentrations of HDL-cholesterol and LDL-cholesterol decreased until ∼2 h (–4 % for both), while TAG concentrations peaked at 3 h (+27 %). Acetoacetate and β-hydroxybutyrate were highest 24 h after the meal (+433 and +633 %, respectively). Acetylcarnitine, butyrylcarnitine, hexanoylcarnitine, octanoylcarnitine, decanoylcarnitine and dodecanoylcarnitine reached the lowest values at 60 min (decreases ranging from –47 to –70 %), before increasing and peaking at 24 h after the meal (increases ranging from +86 to +120 %). Our findings suggest that distinguishing between fasting and non-fasting blood samples falls short of capturing the dynamics in lipid, ketone, carnitine and acylcarnitine concentrations. To enhance the utility of serum acylcarnitine analyses, we strongly recommend accounting for the specific time since the last meal at the time of blood sampling.

• Johansen, Anja Katrin; Bogsrud, Martin Prøven; Thoresen, Magne; Christensen, Jacob J.; Narverud, Ingunn & Langslet, Gisle [Show all 9 contributors for this article] (2024). Lipoprotein(a) in children and adolescents with genetically confirmed familial hypercholesterolemia followed up at a specialized lipid clinic. Atherosclerosis Plus. ISSN 2667-0909. 57, p. 13–18. doi: 10.1016/j.athplu.2024.06.002. Full text in Research Archive Show summary

  Background and aim Many children with an FH mutation also exhibit elevated lipoprotein(a) levels, which is an independent risk factor for atherosclerotic cardiovascular disease. Studies have reported higher levels of lipoprotein(a) in adult and middle-aged women than men. There is limited knowledge on the concentration and change of lipoprotein(a) levels in children with genetic FH, and therefore we investigated sex-differences in lipoprotein(a) level and change in lipoprotein(a) in girls and boys with genetically confirmed FH. Methods Medical records were reviewed retrospectively in 438 subjects with heterozygous FH that started follow-up below the age of 19 years at the Lipid Clinic, Oslo University Hospital in Norway, and of these we included 386 subjects with at least one Lp(a) measurement. Results Mean (SD) age at baseline was 13.8 (7.3) years and the age was similar between sexes. Girls had a higher lipoprotein(a) level than boys at baseline: median (25–75 percentile) 223 (108–487) vs. 154 (78–360) mg/L, respectively (p < 0.01). From baseline to follow-up measurement (mean [SD] 8.9 [6.1] years apart), the mean (95 % CI) absolute and percentage change in Lp(a) level in girls was 151.4 (54.9–247.8) mg/L and 44.8 (16.4–73.1) %, respectively, and in boys it was 66.8 (22.9–110.8) mg/L and 50.5 (8.8–92.3) %, respectively (both p > 0.05). Conclusions We found an increase in Lp(a) levels in children with genetic FH with age, and higher levels in girls than boys, which could impact risk assessment and future ASCVD. Further research is needed to elucidate whether subjects with FH could benefit from lipoprotein(a)-lowering therapies that are under current investigations.

• Olsen, Thomas; Christensen, Jacob Juel; Arnesen, Erik Kristoffer; Lysne, Vegard & Blomhoff, Rune (2024). Preparatory work for the update of the tolerable upper intake levels for vitamin A. EFSA Supporting publication. ISSN 2397-8325. doi: 10.2903/sp.efsa.2024.EN-8651. Full text in Research Archive
• Michelsen, Trond Melbye; Skytte, Hege Nyhus; Gunnes, Nina; Holven, Kirsten Bjørklund; Christensen, Jacob J. & Roland, Marie Cecilie (2024). Metabolic profiles in early pregnancy associated with metabolic pregnancy complications in women with obesity. Journal of Reproductive Immunology. ISSN 0165-0378. 166. doi: 10.1016/j.jri.2024.104397. Full text in Research Archive Show summary

  Introduction Higher maternal body mass index (BMI) is associated with metabolic disturbances and pregnancy complications. We aimed to examine whether metabolic profiles in early pregnancy were associated with metabolic pregnancy complications in women with obesity (BMI ≥ 30 kg/m2). Material and methods Nested cohort study from a prospective longitudinal cohort (n = 1031) of women who were healthy prior to pregnancy and gave birth at Oslo University Hospital from 2002–2008. The sample comprised 81 women with obesity. Metabolic pregnancy complications included gestational diabetes mellitus, gestational hypertension and preeclampsia. In plasma samples from gestational weeks 14–16, 91 metabolites were analyzed by nuclear magnetic resonance spectroscopy. We performed a principal component analysis to reduce the metabolic dimensions. Logistic regression models were fitted to estimate crude and adjusted odds ratios (ORs) of metabolic pregnancy complications. Results Twenty-four out of 81 women developed metabolic pregnancy complications (gestational hypertension, preeclampsia, and/or gestational diabetes). Two of five principal components (80 % explained variance) were significantly associated with metabolic pregnancy complications. The ratio of monounsaturated to total fatty acids increased the risk of metabolic pregnancy complications (OR 2.09, 95 % confidence interval [CI] 1.25–3.75), while the ratio of polyunsaturated to monounsaturated fatty acids decreased the risk (OR 0.54, 95 % CI 0.30–0.89). The ratio of omega-3 to total fatty acids (OR 0.59, 95 % CI 0.34–0.98) and the ratio of docosahexaenoic acid to total fatty acids (OR 0.57, 95 % CI 0.31–0.97) also decreased the risk of metabolic pregnancy complications. Conclusion Metabolic profile in early pregnancy was associated with risk of metabolic pregnancy complications in women with obesity. We observed the strongest associations between fatty acid composition and metabolic pregnancy complications.

• Parlesak, Alexandr; Masino, Talia Theresa; Reis, Kia Daniela; Pettersen, Caroline Filskov; Christensen, Jacob Juel & Olsen, Thomas [Show all 7 contributors for this article] (2024). Preparatory work for the update of the tolerable upper intake levels for iron. EFSA Supporting publication. ISSN 2397-8325. doi: 10.2903/sp.efsa.2024.EN-8661. Full text in Research Archive
• Bålsrud, Pia; Ulven, Stine Marie; Christensen, Jacob J.; Ottestad, Inger & Holven, Kirsten Bjørklund (2024). Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study. BMC Geriatrics. 24(1), p. 1–11. doi: 10.1186/s12877-024-04690-2. Full text in Research Archive Show summary

  Background Low-grade, chronic inflammation during ageing, (“inflammageing”), is suggested to be involved in the development of frailty in older age. However, studies on the association between frailty, using the frailty index definition, and inflammatory markers are limited. The aim of this study was to investigate the relationship between inflammatory markers and frailty index (FI) in older, home-dwelling adults. Method Home-dwelling men and women aged ≥ 70 years old, living in South-East Norway were recruited and included in a cross-sectional study. The FI used in the current study was developed according to Rockwood’s frailty index and included 38 variables, resulting in an FI score between 0 and 1 for each participant. Circulating inflammatory markers (IL-6, CRP, IGF-1, cystatin C, cathepsin S, and glycoprotein Acetyls) were analyzed from non-fasting blood samples using ELISA. Whole-genome PBMC transcriptomics was used to study the association between FI score and inflammation. Results The study population comprised 403 elderly (52% women), with a median age of 74 years and a mean BMI of 26.2 kg/m2. The mean FI score for the total group was 0.15 (range 0.005–0.56). The group was divided into a frail group (FI score ≥ 0.25) and non-frail group. After adjusting for BMI, age, sex, and smoking in the whole group, IL-6, cathepsin S, cystatin C, and Gp-acetyls remained significant associated to FI score (IL-6: 0.002, 95% CI: 0.001, 0.002, cathepsin S: 6.7e-06, 95% CI 2.44e-06, 0.00001, cystatin C: 0.004, 95% CI: 0.002, 0.006, Gp- Acetyls: 0.09, 95% CI: 0.05, 0.13, p < 0.01 for all), while CRP and IGF-1 were not (0.0003, 95% CI: -00001, 0.0007, p = 0.13, (-1.27e-06), 95% CI: (-0.0003), 0.0003, p = 0.99). There was a significant association between FI score and inflammatory markers, and FI score and monocyte-specific gene expression. Conclusions We found an association between FI score and inflammatory markers, and between FI score and monocyte-specific gene expression among elderly subjects above 70 years of age. Whether inflammation is a cause or consequence of frailty and whether the progression of frailty can be attenuated by reducing inflammation remains to be clarified.

• Gregersen, Ida; Narverud, Ingunn; Christensen, Jacob J.; Hovland, Anders Wilhelm; Øyri, Linn Kristin Lie & Ueland, Thor [Show all 11 contributors for this article] (2024). Plasma legumain in familial hypercholesterolemia: associations with statin use and cardiovascular risk markers. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 84(1), p. 24–29. doi: 10.1080/00365513.2024.2309617. Full text in Research Archive Show summary

  Legumain is known to be regulated in atherosclerotic disease and may have both pro- and anti-atherogenic properties. The study aimed to explore legumain in individuals with familial hypercholesterolemia (FH), a population with increased cardiovascular risk. Plasma legumain was measured in 251 subjects with mostly genetically verified FH, of which 166 were adults (≥18 years) and 85 were children and young adults (<18 years) and compared to 96 normolipidemic healthy controls. Plasma legumain was significantly increased in the total FH population compared to controls (median 4.9 versus 3.3 pg/mL, respectively, p < 0.001), whereof adult subjects with FH using statins had higher levels compared to non-statin users (5.7 versus 3.9 pg/mL, respectively, p < 0.001). Children and young adults with FH (p = 0.67) did not have plasma legumain different from controls at the same age. Further, in FH subjects, legumain showed a positive association with apoB, and markers of inflammation and platelet activation (i.e. fibrinogen, NAP2 and RANTES). In the current study, we show that legumain is increased in adult subjects with FH using statins, whereas there was no difference in legumain among children and young adults with FH compared to controls. Legumain was further associated with cardiovascular risk markers in the FH population. However the role of legumain in regulation of cardiovascular risk in these individuals is still to be determined.

• Sousa, Ana Rita Sequeira de; Ottestad, Inger; Gjevestad, Gyrd Omholt; Holven, Kirsten Bjørklund; Ulven, Stine Marie & Christensen, Jacob J. (2023). Associations between PBMC whole genome transcriptome, muscle strength, muscle mass, and physical performance in healthy home-dwelling older women. GeroScience. ISSN 2509-2715. 45, p. 3175–3186. doi: 10.1007/s11357-023-00819-0. Full text in Research Archive Show summary

  Abstract Increasing age is accompanied by many changes, including declining functional skeletal muscle health and immune dysfunction. Peripheral blood mononuclear cells (PBMCs) are circulating cells that assemble an immune response, but their whole genome transcriptome has not been studied in the context of age-related muscle health. Consequently, this article explored associations between three muscle variables indicative of functional muscle health — maximum handgrip strength (muscle strength), appendicular skeletal muscle mass index (ASMI, muscle mass), and gait speed (physical performance) — and two groups of bioinformatics-generated PBMC gene expression features (gene expression–estimated leukocyte subset proportions and gene clusters). We analyzed cross-sectional data from 95 home-dwelling healthy women ≥ 70 years, using “cell-type identification by estimating relative subsets of RNA transcripts” (CIBERSORT) to estimate leukocyte subset proportions and “weighted correlation network analysis” (WGCNA) to generate gene clusters. Associations were studied using linear regression models and relevant gene clusters were subjected to gene set enrichment analysis using gene ontology. Gait speed and ASMI associated with CIBERSORT-estimated monocyte proportions ( β  =  − 0.090, 95% CI = (− 0.146, − 0.034), p -value = 0.002 for gait speed, and β  =  − 0.206, 95% CI = (− 0.385, − 0.028), p -value = 0.024 for ASMI), and gait speed associated with CIBERSORT-estimated M2 macrophage proportions ( β  =  − 0.026, 95% CI = (− 0.043, − 0.008), p -value = 0.004). Furthermore, maximum handgrip strength associated with nine WGCNA gene clusters, enriched in processes related to immune function and skeletal muscle cells ( β in the range − 0.007 to 0.008, p -values &lt; 0.05). These results illustrate interactions between skeletal muscle and the immune system, supporting the notion that age-related functional muscle health and the immune system are closely linked.

• Johansen, Anja Katrin; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Ulven, Stine Marie [Show all 9 contributors for this article] (2023). Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up. Atherosclerosis Plus. ISSN 2667-0909. 51, p. 28–34. doi: 10.1016/j.athplu.2023.01.001. Full text in Research Archive Show summary

  Background and aims The concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0–10, 10–20, 20–30 and >30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD. Methods Data was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time. Results Subjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7–17; 25–75 percentiles, minimum 2), with median 6 (4–9; 25–75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age. Conclusion Our study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.

• Øyri, Linn K. L.; Christensen, Jacob J.; Sebert, Sylvain; Thoresen, Magne; Michelsen, Trond M. & Ulven, Stine M. [Show all 12 contributors for this article] (2023). Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study. BMC Medicine. 21. doi: 10.1186/s12916-023-02742-9. Full text in Research Archive Show summary

  Background Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. Methods This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). Results Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99). Conclusions Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

• Skytte, Hege; Roland, Marie Cecilie; Christensen, Jacob J.; Holven, Kirsten Bjørklund; Lekva, Tove & Gunnes, Nina [Show all 7 contributors for this article] (2023). Maternal metabolic profiling across body mass index groups: An exploratory longitudinal study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 103(3), p. 540–550. doi: 10.1111/aogs.14750. Full text in Research Archive Show summary

  Abstract Introduction Increased BMI has been identified as a risk factor for most pregnancy complications, but the underlying metabolic factors mediating the detrimental effects of BMI are largely unknown. We aimed to compare metabolic profiles in overweight/obese women (body mass index [BMI] ≥ 25 kg/m 2 ) and normal weight/underweight women (BMI &lt; 25 kg/m 2 ) across gestation. We also explored how gestational weight gain (GWG) affected maternal metabolic profiles. Material and methods Exploratory nested case–control study based on a prospective longitudinal cohort of women who were healthy prior to pregnancy and gave birth at Oslo University Hospital from 2002 to 2008. The sample consisted of 48 women who were overweight/obese and 59 normal‐weight/underweight women. Plasma samples from four time points in pregnancy (weeks 14–16, 22–24, 30–32 and 36–38) were analyzed by nuclear magnetic resonance spectroscopy and 91 metabolites were measured. Linear regression models were fitted for each of the metabolites at each time point. Results Overweight or obese women had higher levels of lipids in very‐low‐density lipoprotein (VLDL), total triglycerides, triglycerides in VLDL, total fatty acids, monounsaturated fatty acids, saturated fatty acids, leucine, valine, and total branched‐chain amino acids in pregnancy weeks 14–16 compared to underweight and normal‐weight women. Docosahexaenoic acid and degree of unsaturation were significantly lower in overweight/obese women in pregnancy weeks 36–38. In addition, overweight or obese women had higher particle concentration of XXL‐VLDL and glycoprotein acetyls (GlycA) at weeks 14–16 and 30–32. GWG did not seem to affect the metabolic profile, regardless of BMI group when BMI was treated as a dichotomous variable, ≥25 kg/m 2 (yes/no). Conclusions Overweight or obese women had smaller pregnancy‐related metabolic alterations than normal‐weight/underweight women. There was a trend toward higher triglyceride and VLDL particle concentration in overweight/obese women. As this was a hypothesis‐generating study, the similarities with late‐onset pre‐eclampsia warrant further investigation. The unfavorable development of fatty acid composition in overweight/obese women, with possible implication for the offspring, should also be studied further in the future.

• Lamberg-Allardt, Christel; Adebayo, Folasade; Peltonen, Henna; Christensen, Jacob Juel & Olsen, Thomas (2023). Preparatory work for the update of the tolerable upper intake levels for vitamin D. EFSA Supporting publication. ISSN 2397-8325. doi: 10.2903/sp.efsa.2023.EN-7941. Full text in Research Archive
• Rodriguez-Borjabad, Celia; Narverud, Ingunn; Christensen, Jacob J.; Ibarretxe, Daiana; Andreychuk, Natalia & Girona, Josefa [Show all 13 contributors for this article] (2023). Association between Nordic and Mediterranean diets with lipoprotein phenotype assessed by ¹HNMR in children with familial hypercholesterolemia. Atherosclerosis. ISSN 0021-9150. 373, p. 38–45. doi: 10.1016/j.atherosclerosis.2023.04.009. Full text in Research Archive Show summary

  Background and aims Both Nordic and Mediterranean diets are considered healthy despite notable regional differences. Although these dietary patterns may lower cardiovascular risk, it is unclear if they improve the lipoprotein phenotype in children with familial hypercholesterolemia (FH). The aim is to determine the impact of Nordic and Mediterranean diets on the advanced lipoprotein profile in children with heterozygous FH (HeFH). Methods This was a cross-sectional study performed in children with FH recruited from the Lipid Clinics at Sant Joan University Hospital in Reus (Spain) and Oslo University Hospital (Norway). Two-hundred fifty-six children (mean age 10 y/o; 48% girls): 85 Spanish and 29 Norwegian FH children, and 142 non-FH healthy controls (119 from Spain and 23 from Norway) were included in the study. A pathogenic FH-associated genetic variant was present in 81% of Spanish children with FH and all Norwegian children with FH. An 1H NMR based advanced lipoprotein test (Nightingale®) providing information on the particle number, size and lipid composition of 14 lipoprotein subclasses was performed and correlated to the dietary components. Results Levels of LDL-C, HDL-C and triglycerides were not significantly different between the Nordic and Mediterranean FH groups. Spanish children with FH had more LDL particles, mainly of the large and medium LDL subclasses, than Norwegian FH children. Spanish FH children also had more HDL particles, mainly medium and small, than Norwegian FH children. The mean LDL size of Spanish FH children was larger, while the HDL size was smaller than that of the Norwegian FH children. The HDL particle number and size were the main determinants of differences between the two groups. In Norwegian children with FH, dietary total fat and MUFAs showed a significant correlation with all apolipoprotein B-containing lipoproteins and LDL size, whereas there was no correlation to SFA. A weaker association pattern was observed in the Spanish children. Conclusions The lipoprotein profiles of Spanish and Norwegian children showed differences when studied by 1H NMR. These differences were in part associated with differences in dietary patterns.

• Parnell, Laurence D.; McCaffrey, Kira S.; Brooks, Athena W.; Smith, Caren E.; Lai, Chao-Qiang & Christensen, Jacob J. [Show all 8 contributors for this article] (2023). Rate-Limiting Enzymes in Cardiometabolic Health and Aging in Humans. Lifestyle Genomics. ISSN 2504-3161. 16(1), p. 124–138. doi: 10.1159/000531350. Full text in Research Archive Show summary

  Introduction: Rate-limiting enzymes (RLEs) are innate slow points in metabolic pathways, and many function in bio-processes related to nutrient sensing. Many RLEs carry causal mutations relevant to inherited metabolic disorders. Because the activity of RLEs in cardiovascular health is poorly characterized, our objective was to assess their involvement in cardiometabolic health and disease and where altered biophysical and biochemical functions can promote disease. Methods: A dataset of 380 human RLEs was compared to protein and gene datasets for factors likely to contribute to cardiometabolic disease, including proteins showing significant age-related altered expression in blood and genetic loci with variants that associate with common cardiometabolic phenotypes. The biochemical reactions catalyzed by RLEs were evaluated for metabolites enriched in RLE subsets associating with various cardiometabolic phenotypes. Most significance tests were based on Z-score enrichment converted to p values with a normal distribution function. Results: Of 380 RLEs analyzed, 112 function in mitochondria, and 53 are assigned to inherited metabolic disorders. There was a depletion of RLE proteins known as aging biomarkers. At the gene level, RLEs were assessed for common genetic variants that associated with important cardiometabolic traits of LDL-cholesterol or any of the five outcomes pertinent to metabolic syndrome. This revealed several RLEs with links to cardiometabolic traits, from a minimum of 26 for HDL-cholesterol to a maximum of 45 for plasma glucose. Analysis of these GWAS-linked RLEs for enrichment of the molecular constituents of the catalyzed reactions disclosed a number of significant phenotype-metabolite links. These included blood pressure with acetate (p = 2.2 × 10−4) and NADP+ (p = 0.0091), plasma HDL-cholesterol and triglyceride with diacylglycerol (p = 2.6 × 10−5, 6.4 × 10−5, respectively) and diolein (p = 2.2 × 10−6, 5.9 × 10−6), and waist circumference with &lt;sc&gt;d&lt;/sc&gt;-glucosamine-6-phosphate (p = 1.8 × 10−4). Conclusion: In the context of cardiometabolic health, aging, and disease, these results highlight key diet-derived metabolites that are central to specific rate-limited processes that are linked to cardiometabolic health. These metabolites include acetate and diacylglycerol, pertinent to blood pressure and triglycerides, respectively, as well as diacylglycerol and HDL-cholesterol.

• Rundblad, Amanda; Christensen, Jacob J.; Hustad, Kristin Solheim; Bastani, Nasser Ezzatkhah; Ottestad, Inger & Holven, Kirsten Bjørklund [Show all 7 contributors for this article] (2023). Associations between dietary intake and glucose tolerance in clinical and metabolomics-based metabotypes. Genes & Nutrition. ISSN 1555-8932. 18(3). doi: 10.1186/s12263-023-00721-6. Full text in Research Archive Show summary

  Background Metabotyping is a novel concept to group metabolically similar individuals. Different metabotypes may respond differently to dietary interventions; hence, metabotyping may become an important future tool in precision nutrition strategies. However, it is not known if metabotyping based on comprehensive omic data provides more useful identification of metabotypes compared to metabotyping based on only a few clinically relevant metabolites. Aim This study aimed to investigate if associations between habitual dietary intake and glucose tolerance depend on metabotypes identified from standard clinical variables or comprehensive nuclear magnetic resonance (NMR) metabolomics. Methods We used cross-sectional data from participants recruited through advertisements aimed at people at risk of type 2 diabetes mellitus (n = 203). Glucose tolerance was assessed with a 2-h oral glucose tolerance test (OGTT), and habitual dietary intake was recorded with a food frequency questionnaire. Lipoprotein subclasses and various metabolites were quantified with NMR spectroscopy, and plasma carotenoids were quantified using high-performance liquid chromatography. We divided participants into favorable and unfavorable clinical metabotypes based on established cutoffs for HbA1c and fasting and 2-h OGTT glucose. Favorable and unfavorable NMR metabotypes were created using k-means clustering of NMR metabolites. Results While the clinical metabotypes were separated by glycemic variables, the NMR metabotypes were mainly separated by variables related to lipoproteins. A high intake of vegetables was associated with a better glucose tolerance in the unfavorable, but not the favorable clinical metabotype (interaction, p = 0.01). This interaction was confirmed using plasma concentrations of lutein and zeaxanthin, objective biomarkers of vegetable intake. Although non-significantly, the association between glucose tolerance and fiber intake depended on the clinical metabotypes, while the association between glucose tolerance and intake of saturated fatty acids and dietary fat sources depended on the NMR metabotypes. Conclusion Metabotyping may be a useful tool to tailor dietary interventions that will benefit specific groups of individuals. The variables that are used to create metabotypes will affect the association between dietary intake and disease risk.

• Skytte, Hege; Christensen, Jacob J.; Gunnes, Nina; Holven, Kirsten Bjørklund; Lekva, Tove & Henriksen, Tore [Show all 8 contributors for this article] (2023). Metabolic profiling of pregnancies complicated by preeclampsia: A longitudinal study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 102(3), p. 334–343. doi: 10.1111/aogs.14505. Full text in Research Archive Show summary

  Abstract Introduction Preeclampsia is associated with maternal metabolic disturbances, but longitudinal studies with comprehensive metabolic profiling are lacking. We aimed to determine metabolic profiles across gestation in women who developed preeclampsia compared with women with healthy pregnancies. We also explored the respective effects of body mass index (BMI) and preeclampsia on various metabolic measures. Material and methods We measured 91 metabolites by high‐throughput nuclear magnetic resonance spectroscopy at four time points (visits) during pregnancy (weeks 14–16, 22–24, 30–32 and 36–38). Samples were taken from a Norwegian pregnancy cohort. We fitted a linear regression model for each metabolic measure to compare women who developed preeclampsia ( n  = 38) and healthy controls ( n  = 70). Results Among women who developed preeclampsia, 92% gave birth after 34 weeks of gestation. Compared to women with healthy pregnancies, women who developed preeclampsia had higher levels of several lipid‐related metabolites at visit 1, whereas fewer differences were observed at visit 2. At visit 3, the pattern from visit 1 reappeared. At visit 4 the differences were larger in most subgroups of very‐low‐density lipoprotein particles, the smallest high‐density lipoprotein, total lipids and triglycerides. Total fatty acids were also increased, of which monounsaturated fatty acids and saturated fatty acids showed more pronounced differences. Concentration of glycine tended to be lower in pregnancies with preeclampsia until visit 3, although this was not significant after correction for multiple testing. After adjustment for age, BMI, parity and gestational weight gain, all significant differences were attenuated at visits 1 and 2. The estimates were less affected by adjustment at visits 3 and 4. Conclusions In early pregnancy, the metabolic differences between preeclamptic and healthy pregnancies were primarily driven by maternal BMI, probably representing the women's pre‐pregnancy metabolic status. In early third trimester, several weeks before clinical manifestation, the differences were less influenced by BMI, indicating preeclampsia‐specific changes. Near term, women with preeclampsia developed an atherogenic metabolic profile, including elevated total lipids, very‐low‐density lipoprotein, triglycerides, and total fatty acids.

• Christensen, Jacob J.; Arnesen, Erik Kristoffer; Rundblad, Amanda; Telle-Hansen, Vibeke; Narverud, Ingunn & Blomhoff, Rune [Show all 10 contributors for this article] (2023). Dietary fat quality, plasma atherogenic lipoproteins, and atherosclerotic cardiovascular disease: An overview of the rationale for dietary recommendations for fat intake. Atherosclerosis. ISSN 0021-9150. 389. doi: 10.1016/j.atherosclerosis.2023.117433. Full text in Research Archive Show summary

  The scientific evidence supporting the current dietary recommendations for fat quality keeps accumulating; however, a paradoxical distrust has taken root among many researchers, clinicians, and in parts of the general public. One explanation for this distrust may relate to an incomplete overview of the totality of the evidence for the link between fat quality as a dietary exposure, and health outcomes such as atherosclerotic cardiovascular disease (ASCVD). Therefore, the main aim of the present narrative review was to provide a comprehensive overview of the rationale for dietary recommendations for fat intake, limiting our discussion to ASCVD as outcome. Herein, we provide a core framework – a causal model – that can help us understand the evidence that has accumulated to date, and that can help us understand new evidence that may become available in the future. The causal model for fat quality and ASCVD is comprised of three key research questions (RQs), each of which determine which scientific methods are most appropriate to use, and thereby which lines of evidence that should feed into the causal model. First, we discuss the link between low-density lipoprotein (LDL) particles and ASCVD (RQ1); we draw especially on evidence from genetic studies, randomized controlled trials (RCTs), epidemiology, and mechanistic studies. Second, we explain the link between dietary fat quality and LDL particles (RQ2); we draw especially on metabolic ward studies, controlled trials (randomized and non-randomized), and mechanistic studies. Third, we explain the link between dietary fat quality, LDL particles, and ASCVD (RQ3); we draw especially on RCTs in animals and humans, epidemiology, population-based changes, and experiments of nature. Additionally, the distrust over dietary recommendations for fat quality may partly relate to an unclear understanding of the scientific method, especially as applied in nutrition research, including the process of developing dietary guidelines. We therefore also aimed to clarify this process. We discuss how we assess causality in nutrition research, and how we progress from scientific evidence to providing dietary recommendations.

• Åkesson, Agneta; Söderlund, Fredrik; Bärebring, Linnea; Christensen, Jacob Juel; Olsen, Thomas & Witthöft, Cornelia M (2023). Preparatory work for the update of the tolerable upper intake levels for folic acid/folate. EFSA Supporting publication. ISSN 2397-8325. doi: 10.2903/sp.efsa.2023.EN-7940. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2022). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 32(7), p. 1651–1660. doi: 10.1016/j.numecd.2022.03.028. Full text in Research Archive Show summary

  Familial hypercholesterolemia (FH) is a genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of pre- mature coronary heart disease (CHD). Cholesterol-lowering therapy (statins) reduces CHD risk, but have been available only in the last 25 years, thus, elderly FH patients have been exposed to elevated LDL-C levels most of their life. Surprisingly, some of these have never experienced any CHD event, raising the question whether they present CHD resistant characteristics. Identifying possible cardioprotective biomarkers could contribute to future CHD preventive treatment, therefore, we aimed to identify metabolic markers in event-free elderly FH subjects. Methods and results: We used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify a large number of metabolites in serum samples from 83 FH patients >65 years, and analyze differences between subjects with (n = 39) and without (n = 44) CHD. Mean age was 70 years in both groups (57% and 38% female in the event-free group and CHD group, respectively). The event-free group had significantly higher levels of large and extra-large high-density lipoprotein (HDL) particles, and higher concentration of Apolipoprotein A1 (ApoA1) and cholesterol in HDL and HDL2 particles, compared to the CHD group (p < 0.05 for all). Conclusion: CHD resistant elderly FH patients have higher levels of large HDL particles. The mechanisms behind the event-free survival among these patients remain unclear; hence, a deeper understanding of the metabolic profile in event-free elderly FH subjects may lead to development of novel preventive therapies.

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2022). Use of statins and other lipid-modifying agents across pregnancy: A nationwide drug utilization study in Norway in 2005–2018. Atherosclerosis. ISSN 0021-9150. p. 1–10. doi: 10.1016/j.atherosclerosis.2022.11.022. Full text in Research Archive Show summary

  Background and aims Statins are becoming more widely used among women of reproductive age; however, nationwide data on statin use across pregnancy is scarce. We therefore aimed to describe the drug utilization patterns for statins and other lipid-modifying agents (LMAs) before, during, and after pregnancy, for all pregnancies in Norway from 2005 to 2018. Methods We linked individual-level data from four nationwide electronic health care registries in Norway and characterized the prescription fills of statins and other LMAs across pregnancy. We also examined trends in pregnancy-related LMA use, and characterized women using statins and other LMAs on parameters of health status and co-morbidity. Results In total, 822,071 pregnancies for 503,723 women were included. The number of statin prescription fills decreased rapidly during the first trimester and returned to pre-pregnancy levels about one year postpartum. Pregnancy-related statin use increased from 2005 (approx. 0.11% of all pregnancies) to 2018 (approx. 0.29% of all pregnancies); however, in total, few statin prescriptions were filled within any trimester of pregnancy (n = 331, 0.04% of all pregnancies). Statin use was more common in women with higher age, higher weight, smoking, and comorbidities such as hypertension and diabetes mellitus; also, statin users often had co-medication pertinent to these conditions. Conclusions Although statins and other LMAs were increasingly being used around the time of pregnancy among women in Norway, drug use was mostly discontinued during the first trimester. Our results suggest that pregnancy-related statin use should be monitored, and that drug safety analyses for maternal and offspring health outcomes are needed.

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2022). Use of statins and other lipid-modifying agents across pregnancy – a nationwide drug utilization study of 822 071 pregnancies in Norway in 2005-2018. medRxiv. doi: 10.1101/2022.06.28.22276237. Full text in Research Archive
• Lee, Yu-Chi; Christensen, Jacob Juel; Parnell, Laurence D.; Smith, Caren E.; Shao, Jonathan & McKeown, Nicola M. [Show all 8 contributors for this article] (2022). Using Machine Learning to Predict Obesity Based on Genome-Wide and Epigenome-Wide Gene–Gene and Gene–Diet Interactions. Frontiers in Genetics. 12. doi: 10.3389/fgene.2021.783845. Full text in Research Archive Show summary

  Obesity is associated with many chronic diseases that impair healthy aging and is governed by genetic, epigenetic, and environmental factors and their complex interactions. This study aimed to develop a model that predicts an individual’s risk of obesity by better characterizing these complex relations and interactions focusing on dietary factors. For this purpose, we conducted a combined genome-wide and epigenome-wide scan for body mass index (BMI) and up to three-way interactions among 402,793 single nucleotide polymorphisms (SNPs), 415,202 DNA methylation sites (DMSs), and 397 dietary and lifestyle factors using the generalized multifactor dimensionality reduction (GMDR) method. The training set consisted of 1,573 participants in exam 8 of the Framingham Offspring Study (FOS) cohort. After identifying genetic, epigenetic, and dietary factors that passed statistical significance, we applied machine learning (ML) algorithms to predict participants’ obesity status in the test set, taken as a subset of independent samples (n = 394) from the same cohort. The quality and accuracy of prediction models were evaluated using the area under the receiver operating characteristic curve (ROC-AUC). GMDR identified 213 SNPs, 530 DMSs, and 49 dietary and lifestyle factors as significant predictors of obesity. Comparing several ML algorithms, we found that the stochastic gradient boosting model provided the best prediction accuracy for obesity with an overall accuracy of 70%, with ROC-AUC of 0.72 in test set samples. Top predictors of the best-fit model were 21 SNPs, 230 DMSs in genes such as CPT1A, ABCG1, SLC7A11, RNF145, and SREBF1, and 26 dietary factors, including processed meat, diet soda, French fries, high-fat dairy, artificial sweeteners, alcohol intake, and specific nutrients and food components, such as calcium and flavonols. In conclusion, we developed an integrated approach with ML to predict obesity using omics and dietary data. This extends our knowledge of the drivers of obesity, which can inform precision nutrition strategies for the prevention and treatment of obesity.Clinical Trial Registration: [www.ClinicalTrials.gov], the Framingham Heart Study (FHS), [NCT00005121].

• Canet, Francisco; Christensen, Jacob J.; Victor, Victor M.; Hustad, Kristin Solheim; Ottestad, Inger & Rundblad, Amanda [Show all 11 contributors for this article] (2022). Glycated proteins, glycine, acetate, and monounsaturated fatty acids may act as new biomarkers to predict the progression of type 2 diabetes: Secondary analyses of a randomized controlled trial. Nutrients. 14(23), p. 1–19. doi: 10.3390/nu14235165. Full text in Research Archive Show summary

  Food protein or food-derived peptides may regulate blood glucose levels; however, studies have shown inconsistent results. The aim of the present study was to characterize subgroups of individuals with increased risk of type 2 diabetes (T2D) and to investigate the cardiometabolic effects of fish protein in the same subgroups. We first divided participants into high insuliniAUC and low insuliniAUC subjects based on their insulin incremental area under the curve (iAUC) levels after a 2 h oral glucose tolerance test (OGTT), and secondly based on whether they had received 5.2 g salmon fish protein or placebo for 8 weeks, in a previously conducted randomized controlled trial (RCT). We then profiled these groups by analyzing plasma metabolomics and peripheral blood mononuclear cell (PBMC) gene expression. Compared to the low insuliniAUC group, the high insuliniAUC group had higher plasma concentrations of monounsaturated fatty acids (MUFAs) and glycated proteins (GlycA) and lower concentrations of glycine and acetate. After intervention with fish protein compared to placebo, however, only acetate was significantly increased in the low insuliniAUC group. In conclusion, we identified metabolic biomarkers known to be associated with T2D; also, intervention with fish protein did not affect cardiometabolic risk markers in subgroups with increased risk of T2D.

• Høyer, Anne; Christensen, Jacob J.; Arnesen, Erik Kristoffer; Andersen, Rikke; Eneroth, Hanna & Erkkola, Maijaliisa [Show all 13 contributors for this article] (2021). The Nordic Nutrition Recommendations 2022 – prioritisation of topics for de novo systematic reviews. Food & Nutrition Research (FNR). ISSN 1654-6628. 65. doi: 10.29219/fnr.v65.7828. Full text in Research Archive
• Rodriguez-Borjabad, Celia; Narverud, Ingunn; Christensen, Jacob J.; Ulven, Stine Marie; Malo, Ana Irene & Ibarretxe, Daiana [Show all 13 contributors for this article] (2021). Dietary intake and lipid levels in Norwegian and Spanish children with familial hypercholesterolemia. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 31(4), p. 1299–1307. doi: 10.1016/j.numecd.2020.12.002. Full text in Research Archive
• Larsen, Sunniva Veen; Holven, Kirsten B.; Christensen, Jacob J.; Flatberg, Arnar; Rundblad, Amanda & Leder, Lena [Show all 13 contributors for this article] (2021). Replacing Saturated Fat with Polyunsaturated Fat Modulates Peripheral Blood Mononuclear Cell Gene Expression and Pathways Related to Cardiovascular Disease Risk Using a Whole Transcriptome Approach. Molecular Nutrition & Food Research. ISSN 1613-4125. 65(24). doi: 10.1002/mnfr.202100633. Full text in Research Archive Show summary

  The aim of this study is to explore the molecular mechanisms underlying the effect of replacing dietary saturated fat (SFA) with polyunsaturated fat (PUFA) on cardiovascular disease (CVD) risk using a whole transcriptome approach. Methods and Results Healthy subjects with moderate hypercholesterolemia (n = 115) are randomly assigned to a control diet (C-diet) group or an experimental diet (Ex-diet) group receiving comparable food items with different fatty acid composition for 8 weeks. RNA isolated from peripheral blood mononuclear cells (PBMCs) at baseline and after 8 weeks of intervention is analyzed by microarray technology (n = 95). By use of a linear regression model (n = 92), 14 gene transcripts are differentially altered in the Ex-diet group compared to the C-diet group. These include transcripts related to vascular smooth muscle cell proliferation, low-density lipoprotein receptor folding, and regulation of blood pressure. Furthermore, pathways mainly related to immune response and inflammation, signal transduction, development, and cytoskeleton remodeling, gene expression and protein function, are differentially enriched between the groups. Conclusion Replacing dietary SFA with PUFA for 8 weeks modulates PBMC gene expression and pathways related to CVD risk in healthy subjects with moderate hypercholesterolemia.

• Øyri, Linn Kristin Lie; Bogsrud, Martin Prøven; Christensen, Jacob J.; Ulven, Stine Marie; Brantsæter, Anne Lise & Retterstøl, Kjetil [Show all 13 contributors for this article] (2021). Novel associations between parental and newborn cord blood metabolic profiles in the Norwegian Mother, Father and Child Cohort Study. BMC Medicine. 19(19). doi: 10.1186/s12916-021-01959-w. Full text in Research Archive Show summary

  Background:More than one third of Norwegian women and men between 20 and 40 years of age have elevated cholesterol concentration. Parental metabolic health around conception or during pregnancy may affect the offspring’s cardiovascular disease risk. Lipids are important for fetal development, but the determinants of cord blood lipids have scarcely been studied. We therefore aimed to describe the associations between maternal andpaternal peri-pregnancy lipid and metabolic profile and newborn cord blood lipid and metabolic profile. Methods:This study is based on 710 mother–father–newborn trios from the Norwegian Mother, Father and ChildCohort Study (MoBa) and uses data from the Medical Birth Registry of Norway (MBRN). The sample included in thisstudy consisted of parents with and without self-reported hypercholesterolemia the last 6 months before pregnancy and their partners and newborns. Sixty-four cord blood metabolites detected by nuclear magnetic resonance spectroscopy were analyzed by linear mixed model analyses. The false discovery rate procedure wasused to correct for multiple testing. Results:Among mothers with hypercholesterolemia, maternal and newborn plasma high-density lipoproteincholesterol, apolipoprotein A1, linoleic acid, docosahexaenoic acid, alanine, glutamine, isoleucine, leucine, valine,creatinine, and particle concentration of medium high-density lipoprotein were significantly positively associated(0.001≤q≤0.09). Among mothers without hypercholesterolemia, maternal and newborn linoleic acid, valine,tyrosine, citrate, creatinine, high-density lipoprotein size, and particle concentration of small high-density lipoproteinwere significantly positively associated (0.02≤q≤0.08). Among fathers with hypercholesterolemia, paternal andnewborn ratio of apolipoprotein B to apolipoprotein A1 were significantly positively associated (q= 0.04). Amongfathers without hypercholesterolemia, no significant associations were found between paternal and newbornmetabolites. Sex differences were found for many cord blood lipids. Conclusions:Maternal and paternal metabolites and newborn sex were associated with several cord bloodmetabolites. This may potentially affect the offspring’s long-term cardiovascular disease risk.Keywords:MoBa, the Norwegian Mother, Father and Child Cohort Study, MBRN, Medical Birth Registry of Norway,Cholesterol, Metabolic profiling, Cord blood, Sex differences

• Christensen, Jacob J.; Narverud, Ingunn; Ruuth, Maija; Heier, Martin; Jauhiainen, Matti & Ulven, Stine Marie [Show all 14 contributors for this article] (2021). Children with familial hypercholesterolemia display changes in LDL and HDL function: A cross-sectional study. Journal of Internal Medicine. ISSN 0954-6820. 290(5), p. 1083–1097. doi: 10.1111/joim.13383. Full text in Research Archive
• Arnesen, Erik Kristoffer; Christensen, Jacob Juel; Andersen, Rikke; Eneroth, Hanna; Erkkola, Maijaliisa & Høyer, Anne [Show all 13 contributors for this article] (2020). The Nordic Nutrition Recommendations 2022 – structure and rationale of qualified systematic reviews. Food & Nutrition Research (FNR). ISSN 1654-6628. 64, p. 1–11. doi: 10.29219/fnr.v64.4403. Full text in Research Archive Show summary

  Background: Qualified systematic reviews (SRs) will form the main basis for evaluating causal effects of nutrients or food groups on health outcomes in the sixth edition of Nordic Nutrition Recommendations to be published in 2022 (NNR2022). Objective: To describe rationale and structure of SRs used in NNR2022. Design: The SR methodologies of the previous edition of NNR were used as a starting point. Methodologies of recent SRs commissioned by leading national food and health authorities or international food and health organizations were examined and scrutinized. Methodologies for developing SRs were agreed by the NNR2022 Committee in a consensus-driven process. Results: Qualified SRs will be developed by a cross-disciplinary group of experts and reported according to the requirements of the EQUATOR network. A number of additional requirements must also be fulfilled, including 1) a clearly stated set of objectives and research questions with pre-defined eligibility criteria for the studies, 2) an explicit, reproducible methodology, 3) a systematic search that attempts to identify all studies that would meet the eligibility criteria, 4) an assessment of the validity of the findings of the included studies through an assessment of ‘risk of bias’ of the studies, 5) a systematic presentation and synthesis of the characteristics and findings of the included studies, and 6) a grading of the overall evidence. The complete definition and requirements of a qualified SR are described. Discussion: Most SRs published in scientific journals do not fulfill all criteria of the qualified SRs in the NNR2022 project. This article discusses the structure and rationale for requirements of qualified SRs in NNR2022. National food and health authorities have only recently begun to use qualified SRs as a basis for nutrition recommendations. Conclusion: Qualified SRs will be used to inform dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the NNR2022 project.

• Christensen, Jacob Juel; Arnesen, Erik Kristoffer; Andersen, Rikke; Eneroth, Hanna; Erkkola, Maijaliisa & Høyer, Anne [Show all 13 contributors for this article] (2020). The Nordic Nutrition Recommendations 2022 – Principles and Methodologies. Food & Nutrition Research (FNR). ISSN 1654-6628. 64, p. 1–15. doi: 10.29219/fnr.v64.4402. Full text in Research Archive Show summary

  Background: The Nordic Nutrition Recommendations (NNRs) constitute the scientific basis for national dietary reference values (DRVs) and food-based dietary guidelines (FBDGs) in the Nordic and Baltic countries. Objective: To define principles and methodologies for the sixth edition of NNR to be published in 2022 (NNR2022). Design: The principles and methodologies of the previous edition of NNR were used as a starting point. Recent nutrition recommendations commissioned by other national food and health authorities or international food and health organizations were examined and dissected. Updated principles and methodologies were agreed by the NNR2022 Committee in a consensus-driven process. Results: An organizational model with ‘checks and balances’ was developed to minimize the influence of subjective biases of the committee members and experts. Individual chapters on all included nutrients and food groups will be updated as scoping reviews. Systematic reviews (SRs), which are the main basis for evaluating causal effects of nutrients or food groups on health outcomes, will be embedded in each chapter. A NNR SR Centre will be established for performing de novo SRs on prioritized topics. To avoid duplication and optimize the use of resources, qualified SRs commissioned by other national and international organizations and health authorities will also inform DRVs and FBDGs in NNR2022. Discussion: The evidence-based methods defined in the NNR2022 project are compatible with most contemporary methods used by leading national food and health authorities. Global harmonization of methodological approaches to nutrition recommendations is strongly encouraged. Conclusion: Evidence-informed principles and methodologies underpinned by SRs will ensure that DRVs and FBDGs defined in the NNR2022 project are based on the best available evidence and as far as possible free from overt bias.

• Arnesen, Erik Kristoffer; Christensen, Jacob J.; Andersen, Rikke; Eneroth, Hanna; Erkkola, Maijaliisa & Høyer, Anne [Show all 13 contributors for this article] (2020). The nordic nutrition recommendations 2022 – handbook for qualified systematic reviews. Food & Nutrition Research (FNR). ISSN 1654-6628. 64, p. 1–15. doi: 10.29219/fnr.v64.4404. Full text in Research Archive Show summary

  Background: Systematic reviews (SRs) constitute a major part of the Nordic Nutrition Recommendations (NNRs). The step-by-step procedure used to develop SRs has evolved considerably over time and is often tailored to fit the exposure and outcomes in focus. Objective: To describe a detailed procedure for developing qualified SRs commissioned by the NNR2022 project. Design: Scrutinizing procedures of recent SRs commissioned by leading national food and health authorities or international food and health organizations. Results: The following eight steps must be included when developing qualified SRs for the NNR2022 project: 1) define research question, 2) protocol development, 3) literature search, 4) screening and selection of studies, 5) data extraction, 6) assessing risk of bias, 7) synthesis and grading of total strength of evidence, and 8) reporting according to certain standards. Discussion: This guide is based on the guidelines developed for the fifth edition of NNR but includes some important new domains in order to adhere to more recent, authoritative standards. Conclusion: All qualified SRs in the NNR2022 project will follow the protocol described here.

• Christensen, Jacob Juel; Ulven, Stine Marie; Thoresen, Magne; Westerman, Kenneth; Holven, Kirsten Bjørklund & Andersen, Lene Frost (2020). Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: a cross-sectional study (preprint). BioRxiv. ISSN 0362-4331. doi: 10.1101/2020.01.25.20018465. Full text in Research Archive
• Christensen, Jacob J.; Narverud, Ingunn; Ruuth, Maija; Heier, Martin; Ulven, Stine Marie & Bogsrud, Martin Prøven [Show all 12 contributors for this article] (2020). Children with familial hypercholesterolemia display changes in LDL and HDL function: a cross-sectional study. medRxiv. doi: 10.1101/2020.11.11.20214247. Full text in Research Archive Show summary

  Background The functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma LDL particles to aggregate and the ability of HDL particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations. Hypothesis We hypothesized that FH children had disrupted lipoprotein function. Methods We analyzed LDL aggregation susceptibility and HDL-apoA-I exchange to apoA-I ratio (HAE/apoA-I ratio), and activity of four proteins that regulate lipoprotein metabolism (CETP, LCAT, PLTP and PON1) in plasma samples derived from children with FH (n = 47) and from healthy children (n = 56). Potential biological mechanisms behind any variation in lipoprotein functionalities were explored using an NMR-based metabolomics profiling approach. Results LDL aggregation was higher and HAE/apoA-I ratio was lower in FH children than in healthy children. LDL aggregation associated positively with LDL-C and negatively with triglycerides, and HAE/apoA-I ratio associated negatively with LDL-C. Generally, the metabolomic profile for LDL aggregation was a mirror image of that for HAE/apoA-I ratio. Conclusions FH children displayed increased atherogenicity of LDL and disrupted HDL function. These newly observed functional alterations in LDL and HDL may increase the risk for atherosclerotic cardiovascular disease in FH children.

• Thorsteinsdottir, Hjørdis; Christensen, Jacob J.; Holven, Kirsten Bjørklund; Tveiterås, Målfrid; Brun, Henrik & Åsberg, Anders [Show all 7 contributors for this article] (2020). Cardiovascular risk factors are inversely associated with omega-3 polyunsaturated fatty acid plasma levels in pediatric kidney transplant recipients. Journal of renal nutrition. ISSN 1051-2276. 31(3), p. 278–285. doi: 10.1053/j.jrn.2020.06.002. Full text in Research Archive Show summary

  Objectives High plasma levels of the omega-3 fatty acids eicosapentaenoic acid (EPA), docosahexaenoic acid, and docosapentaenoic acid associates with positive outcomes in adult renal transplant recipients. However, data from pediatric populations are scarce. The aim of the study was to assess the fatty acid profile in a pediatric renal transplantation cohort and to examine the associations between plasma omega-3 fatty acids and cardiovascular disease (CVD) risk factors. Methods In this cross-sectional study comprising 53 children (median age, 12.2 years; 32 boys) with a renal transplant, we assessed the prevalence of CVD risk factors as well as markers of end organ damage: carotid intima-media thickness (cIMT) and left ventricular mass index. The associations between plasma omega-3 fatty acids and CVD risk factors were assessed. Results Twenty-five (47%) patients were preemptively transplanted. Seventy-six percent had dyslipidemia and 51% had hypertension. The mean left ventricular mass index was 40.4 ± 14.3 g/m 2.7, and 14% had left ventricular hypertrophy. The mean cIMT was 0.41 ± 0.04 mm. In a multivariate linear regression, EPA levels were inversely associated to blood pressure (β coeff. = −0.37, P = .007), triglycerides (β coeff. = −0.44, P = .01), and high-density lipoprotein cholesterol (β coeff. = −0.41, P = .01). Conclusion EPA levels are inversely associated with components of the metabolic syndrome, which may provide support for specific dietary advice or supplementation in this patient population. cIMT is less pronounced in our cohort than in comparable cohorts with lower rate of preemptive transplantations. Our results need replication in prospective cohorts.

• Christensen, Jacob Juel; Ulven, Stine Marie; Thoresen, Magne; Westerman, Kenneth; Holven, Kirsten Bjørklund & Andersen, Lene Frost (2020). Associations between dietary patterns and gene expression pattern in peripheral blood mononuclear cells: A cross-sectional study. NMCD. Nutrition Metabolism and Cardiovascular Diseases. ISSN 0939-4753. 30(11), p. 2111–2122. doi: 10.1016/j.numecd.2020.06.018. Full text in Research Archive Show summary

  Background and aims Diet may alter gene expression in immune cells involved in atherosclerotic cardiovascular disease susceptibility. However, we still lack a robust understanding of the association between diet and immune cell-related gene expression in humans. Therefore, we examined associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults (n = 130 women and 105 men). Methods and results We used factor analysis to define a posteriori DPs from food frequency questionnaire-based dietary assessment data. In addition, we derived interpretable features from microarray-based gene expression data (13 967 transcripts) using two algorithms: CIBERSORT for estimation of cell subtype proportions, and weighted gene co-expression network analysis (WGCNA) for cluster discovery. Finally, we associated DPs with either CIBERSORT-predicted PBMC leukocyte distribution or WGCNA gene clusters using linear regression models. We detected three DPs that broadly reflected Western, Vegetarian, and Low carbohydrate diets. CIBERSORT-predicted percentage of monocytes associated negatively with the Vegetarian DP. For women, the Vegetarian DP associated with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription, whereas for men, the Western DP inversely associated with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes. A subsequent protein–protein interaction network analysis suggested that genes within these clusters might physically interact in biological networks. Conclusions Although the present findings are exploratory, our analysis pipeline serves as a useful framework for studying the association between diet and gene expression.

• Mangano, Kelsey M.; Noel, Sabrina E.; Lai, Chao-Qiang; Christensen, Jacob Juel; Ordovas, Jose M & Dawson-Hughes, Bess [Show all 8 contributors for this article] (2020). Diet-derived fruit and vegetable metabolites show sex-specific inverse relationships to osteoporosis status. Bone. ISSN 8756-3282. 144. doi: 10.1016/j.bone.2020.115780. Full text in Research Archive
• Telle-Hansen, Vibeke; Christensen, Jacob J.; Formo, Gulla Aase; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2020). A comprehensive metabolic profiling of the metabolically healthy obesity phenotype. Lipids in Health and Disease. 19, p. 1–12. doi: 10.1186/s12944-020-01273-z. Full text in Research Archive Show summary

  Background: The ever-increasing prevalence of obesity constitutes a major health problem worldwide. A subgroup of obese individuals has been described as “metabolically healthy obese” (MHO). In contrast to metabolically unhealthy obese (MUO), the MHO phenotype has a favorable risk profile. Despite this, the MHO phenotype is still sub-optimally characterized with respect to a comprehensive risk assessment. Our aim was to increase the understanding of metabolic alterations associated with healthy and unhealthy obesity. Methods: In this cross-sectional study, men and women (18–70years) with obesity (body mass index (BMI)≥30kg/ m2) or normal weight (NW) (BMI≤25kg/m2) were classified with MHO (n=9), MUO (n=10) or NW (n=11) according to weight, lipid profile and glycemic regulation. We characterized individuals by comprehensive metabolic profiling using a commercial available high-throughput proton NMR metabolomics platform. Plasma fatty acid profile, including short chain fatty acids, was measured using gas chromatography. Results: The concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) subclasses were overall significantly higher, and high density lipoprotein (HDL) subclasses lower in MUO compared with MHO. VLDL and IDL subclasses were significantly lower and HDL subclasses were higher in NW compared with MHO. The concentration of isoleucine, leucine and valine was significantly higher in MUO compared with MHO, and the concentration phenylalanine was lower in NW subjects compared with MHO. The fatty acid profile in MHO was overall more favorable compared with MUO. Conclusions: Comprehensive metabolic profiling supports that MHO subjects have intermediate-stage cardiovascular disease risk marker profile compared with NW and MUO subjects. Clinical trial registration number: NCT01034436, Fatty acid quality and overweight (FO-study).

• Hustad, Solheim Kristin; Rundblad, Amanda; Ottestad, Inger; Christensen, Jacob J.; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2020). Comprehensive lipid and metabolite profiling in healthy adults with low and high consumption of fatty fish: A cross-sectional study. British Journal of Nutrition. ISSN 0007-1145. p. 1–9. doi: 10.1017/S0007114520002305. Full text in Research Archive Show summary

  Abstract Fish consumption is associated with reduced risk of CVD, which may be partly mediated by alterations in plasma lipids, such as HDL-cholesterol. However, comprehensive analyses of associations between fatty fish consumption and lipoprotein subclass profile are limited and show inconsistent results. Therefore, the aim of the present exploratory study was to investigate the association between fatty fish consumption and lipoprotein subclass particle concentrations and composition, with an emphasis on HDL. We performed a comprehensive plasma metabolite profiling in 517 healthy adults, using a targeted high-throughput NMR spectroscopy platform. The participants were divided into tertiles based on consumption of fatty fish, reported through a validated FFQ. We compared the concentration of metabolites between the participants in the lowest and highest tertiles of fatty fish consumption. We show that high consumers of fatty fish (&gt;223 g/week, median intake 294 g/week) had higher particle concentrations and content of total lipids, free cholesterol and phospholipids in large and extra-large HDL particles and higher content of total cholesterol, cholesteryl esters and TAG in large HDL particles than low consumers (&lt;107 g/week, median intake 58 g/week). Using fatty fish consumption as a continuous variable, we found that fatty fish consumption was associated with lower levels of the inflammation marker glycoprotein acetyls. In conclusion, high consumers of fatty fish seem to have a more favourable HDL-cholesterol-related lipoprotein profile and anti-inflammatory phenotype than low consumers of fatty fish. Thus, these data support the current Norwegian dietary recommendations for fish consumption regarding CVD risk.

• Christensen, Jacob J.; Bakke, Siril Skaret; Ulven, Stine Marie; Retterstøl, Kjetil; Henriksen, Tore & Bollerslev, Jens [Show all 10 contributors for this article] (2019). Serum Omega-6 Fatty Acids and Immunology-Related Gene Expression in Peripheral Blood Mononuclear Cells: A Cross-Sectional Analysis in Healthy Children. Molecular Nutrition & Food Research. ISSN 1613-4125. 63(7). doi: 10.1002/mnfr.201800990. Full text in Research Archive Show summary

  Scope Some studies suggest that a high dietary intake of omega‐6 fatty acids is pro‐inflammatory. However, whether omega‐6 fatty acids actually cause pathogenic inflammation in humans is debated. Therefore, the associations between expression of immunology‐related genes in peripheral blood mononuclear cells (PBMCs) and serum total omega‐6 PUFA status are investigated. Methods and results Serum fatty acid profile and expression of 460 immunology‐related genes in PBMCs from 58 healthy children (6–13 years) is measured, and examined the expression differences between children with high or low total omega‐6 PUFA status (upper vs lower tertile). Taken together, both univariate analyses and integrated omics analyses support that while high omega‐6 PUFA level associated with higher expressing of genes related to innate immune responses, it also associated with lower expression of several genes related to adaptive immune responses. Conclusion Omega‐6 PUFA status associated both positively and negatively with expression of specific immunology‐related genes in PBMCs in healthy children. The results may suggest a nuanced role for omega‐6 fatty acids in the interphase of lipids and inflammation, and warrants further examination in gene‐environment studies and randomized controlled trials.

• Ulven, Stine Marie; Christensen, Jacob J.; Nygård, Ottar; Svardal, Asbjørn M.; Leder, Lena & Ottestad, Inger [Show all 14 contributors for this article] (2019). Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat-a randomized controlled dietary intervention study. American Journal of Clinical Nutrition. ISSN 0002-9165. 109(5), p. 1239–1250. doi: 10.1093/ajcn/nqy356. Full text in Research Archive Show summary

  Background: Replacing dietary saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFA) reduces the plasma low-density lipoprotein (LDL) cholesterol and subsequently the risk of cardiovascular disease. However, beyond changes in LDL cholesterol, we lack a complete understanding of the physiologic alterations that occur when improving dietary fat quality. Objectives: The aim of this study was to gain knowledge of metabolic alterations paralleling improvements in the fat quality of the diet. Methods: We recently conducted an 8-wk, double-blind, randomized controlled trial replacing SFAs with PUFAs in healthy subjects with moderate hypercholesterolemia (n = 99). In the present substudy, we performed comprehensive metabolic profiling with multiple platforms (both nuclear magnetic resonance- and mass spectrometry-based technology) (n = 99), and analyzed peripheral blood mononuclear cell gene expression (n = 95) by quantitative real-time polymerase chain reaction. Results: A large number of lipoprotein subclasses, myristoylcarnitine and palmitoylcarnitine, and kynurenine were reduced when SFAs were replaced with PUFAs. In contrast, bile acids, proprotein convertase subtilisin/kexin type 9, acetate, and acetoacetate were increased by the intervention. Some amino acids were also altered by the intervention. The mRNA levels of LXRA and LDLR were increased, in addition to several liver X receptor α target genes and genes involved in inflammation, whereas the mRNA levels of UCP2 and PPARD were decreased in peripheral blood mononuclear cells after replacing SFAs with PUFAs. Partial least squares-discriminant analysis showed that the 30 most important variables that contributed to class separation spanned all classes of biomarkers, and was in accordance with the univariate analysis. Conclusions: Applying metabolomics in randomized controlled dietary intervention trials has the potential to extend our knowledge of the biological and molecular effects of dietary fat quality. This study was registered at clinicaltrials.gov as NCT 01679496.

• Narverud, Ingunn; Christensen, Jacob J.; Bakke, Siril Skaret; Ulven, Stine Marie; Rundblad, Amanda & Aukrust, Pål [Show all 12 contributors for this article] (2019). Profiling of immune-related gene expression in children with familial hypercholesterolaemia. Journal of Internal Medicine. ISSN 0954-6820. p. 1–12. doi: 10.1111/joim.13001. Full text in Research Archive Show summary

  Background Innate and adaptive immune responses are pivotal in atherosclerosis, but their association with early‐stage atherosclerosis in humans is incompletely understood. In this regard, untreated children with familial hypercholesterolaemia may serve as a human model to investigate the effect of elevated low‐density lipoprotein (LDL)‐cholesterol. Objectives We aimed to study the immunological and inflammatory pathways involved in early atherosclerosis by examining mRNA molecules in peripheral blood mononuclear cells (PBMCs) from children with FH. Methods We analysed the level of 587 immune‐related mRNA molecules using state‐of‐the‐art Nanostring technology in PBMCs from children with (n = 30) and without (n = 21) FH, and from FH children before and after statin therapy (n = 10). Results 176 genes (30%) were differentially expressed between the FH and healthy children at P < 0.05. Compared to healthy children, the dysregulated pathways in FH children included the following: T cells (18/19); B cells (5/6); tumour necrosis factor super family (TNFSF) (6/8); cell growth, proliferation and differentiation (5/7); interleukins (5/9); toll‐like receptors (2/5); apoptosis (3/7) and antigen presentation (1/7), where the ratio denotes higher expressed genes to total number of genes. Statin therapy reversed expression of thirteen of these mRNAs in FH children. Conclusion FH children display higher PBMC expression of immune‐related genes mapped to several pathways, including T and B cells, and TNFSF than healthy children. Our results suggest that LDL‐C plays an important role in modulating expression of different immune‐related genes, and novel data on the involvement of these pathways in the early atherosclerosis may represent future therapeutic targets for prevention of atherosclerotic progression.

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• Christensen, Jacob J. (2025). Toksisitet ved høyt inntak av vitamin D. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 23(2), p. 90–96. doi: 10.18261/ntfe.23.2.5. Full text in Research Archive Show summary

  Høyt inntak av vitamin D kan føre til toksisitet. Dette ble aktualisert i forbindelse med en tilbakekalling av egg vinteren 2025, der egg inneholdt nivåer av vitamin D opptil 100 ganger normalen. Folkehelseinstituttet (FHI) fastsatte trygge inntaksgrenser for ulike aldersgrupper, og advarte mot symptomer på akutt vitamin D-forgiftning. Det europeiske mattrygghetsorganet (EFSA) har etablert en øvre grense for vitamin D-inntak på 100 µg/dag for voksne, basert på risikoen for hyperkalsemi og hyperkalsiuri. Undersøkelser viser at inntak opp til 250 µg/dag trolig ikke har økt risiko for vedvarende helseproblemer, mens det er veletablert at inntak over 500 µg/dag forårsaker toksisitet. Ved høyt inntak av vitamin D og samtidige symptomer på toksisitet er det aktuelt å oppsøke lege blant annet for å måle kalsium i blodet. Anbefalt inntak (recommended intake, RI) for vitamin D ligger på 10 µg/dag for voksne, med en øvre grense (upper level, UL) på 100 µg/dag for å unngå helseskader.

• Haugan, Malin H.; Grødeland, Gunnveig & Christensen, Jacob J. (2024). Kosttilskudd: - Nå advarer vi folk mot å ta det. [Journal]. KK. Full text in Research Archive
• Blomhoff, Rune; Arnesen, Erik Kristoffer & Christensen, Jacob J. (2024). De nye nordiske kostrådene bygger på solide systematiske kunnskapsoppsummeringer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(1), p. 1–4. doi: 10.4045/tidsskr.23.0814. Full text in Research Archive
• Staude, Vår; Grødeland, Gunnveig & Christensen, Jacob J. (2024). God morgen, Norge: Intervju om hvordan styrke immunsystemet. [TV]. TV2. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Christensen, Jacob J. (2023). From puzzle pieces to picture: Genetic data helps refine our understanding of the link between liver fat and heart disease risk. Atherosclerosis. ISSN 0021-9150. doi: 10.1016/j.atherosclerosis.2023.117410. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2023). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. Full text in Research Archive
• Rundblad, Amanda; Hansen, Anna Lena; Christensen, Jacob Juel; Melnes, Torunn; Ottestad, Inger Olaug & Narverud, Ingunn [Show all 12 contributors for this article] (2023). Patients with familial hypercholesterolemia have shorter telomeres than controls in older, but not in young subjects: a cross-sectional study. Full text in Research Archive
• Rundblad, Amanda; Christensen, Jacob Juel; Hustad, Kristin Solheim; Bastani, Nasser Ezzatkhah; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2023). Associations between dietary intake and glucose tolerance in  clinical and metabolomics-based metabotypes. Full text in Research Archive
• Ulven, Stine Marie; Ottestad, Inger Olaug; Christensen, Jacob Juel & Holven, Kirsten Bjørklund (2023). Inflammatory markers and frailty in home-dwelling elderly, a cross-sectional study. Full text in Research Archive
• Christensen, Jacob Juel; Blomhoff, Rune & Arnesen, Erik Kristoffer (2023). Rødt kjøtt i NNR2023: hvorfor 350 gram per uke? doi: 10.18261/ntfe.21.4.5. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Christensen, Jacob J.; Rundblad, Amanda; Narverud, Ingunn & Retterstøl, Kjetil [Show all 10 contributors for this article] (2023). Difference in PBMC gene expression between elderly event-free FH patients and FH patients with CHD. Full text in Research Archive
• Holven, Kirsten Bjørklund; Ulven, Stine Marie; Ottestad, Inger Olaug & Christensen, Jacob Juel (2023). Inflammatory markers and frailty markers in home-dwelling elderly, a cross-sectional study. Full text in Research Archive
• Holven, Kirsten Bjørklund; Ulven, Stine Marie; Christensen, Jacob Juel & Ottestad, Inger Olaug (2023). Betydning av kosten for endring i skrøpelighet hos hjemmeboende eldre etter 8 års oppfølging. Full text in Research Archive
• Christensen, Jacob Juel (2022). Skulle gjerne ha gått ned tre-fire kilo – hvordan gjør jeg det? Lommelegen.no. Full text in Research Archive Show summary

  https://www.lommelegen.no/overvekt/artikkel/skulle-gatt-ned-tre-fire-kilo-hvordan-gjor-jeg-det/75246786

• Christensen, Jacob Juel (2022). The HADL hypothesis – a helpful addition or just noise? Considering the evidence. Full text in Research Archive
• Telle-Hansen, Vibeke; Christensen, Jacob J.; Formo, Gulla Aase; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2022). Do All People With Obesity Have Increased Risk of Disease? Frontiers for Young Minds. 10. doi: 10.3389/frym.2022.792630. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2022). What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2021). Event-free FH patients ≥65 years of age are characterized by higher concentration of large HDL particles. Full text in Research Archive
• Christensen, Jacob Juel & Lofthus, Elisabeth (2021). Høyt kolesterol? Unngå disse matvarene. Lommelegen.no. Full text in Research Archive
• Christensen, Jacob Juel & Høstmark, Cecilie Bakken (2021). – Du bør fortsatt unngå mettet fett i maten. Forskning.no. ISSN 1891-635X. Full text in Research Archive Show summary

  https://forskning.no/hjertet-mat-og-helse-partner/du-bor-fortsatt-unnga-mettet-fett-i-maten/1896484

• Christensen, Jacob Juel (2021). Ny hypotese fra norske forskere skaper forvirring. FH-magasinet. Full text in Research Archive Show summary

  http://www.f-h.no/informasjon/ny-hypotese-fra-norske-forskere-skaper-forvirring

• Christensen, Jacob Juel & Tømmerbakke, Siri Gulliksen (2021). Norske forskere «krangler» om kostråd i prestisjetidsskrift. Dagens medisin. ISSN 1501-4290. Full text in Research Archive Show summary

  https://www.dagensmedisin.no/artikler/2021/07/06/norske-forskere-krangler-om-kostholdsrad-i-prestisjetidsskrift/

• Christensen, Jacob Juel; Narverud, Ingunn; Ruuth, Maija; Heier, Martin; Jauhiainen, Matti & Ulven, Stine Marie [Show all 14 contributors for this article] (2021). Children with FH display changes in LDL and HDL function: a cross-sectional study. Full text in Research Archive
• Christensen, Jacob Juel (2021). Tre grunner til at det er så vanskelig å gå ned i vekt. Lommelegen.no. Full text in Research Archive Show summary

  https://www.lommelegen.no/overvekt/artikkel/tre-grunner-til-at-det-er-sa-vanskelig-a-ga-ned-i-vekt/74939276

• Christensen, Jacob Juel; Bogsrud, Martin Prøven; Holven, Kirsten Bjørklund; Retterstøl, Kjetil; Veierød, Marit Bragelien & Nordeng, Hedvig Marie Egeland (2021). Maternal use of statins in pregnancy: a population based registry study. Full text in Research Archive
• Christensen, Jacob Juel (2021). The HADL hypothesis – a helpful addition or just noise? Considering the evidence. Full text in Research Archive
• Christensen, Jacob Juel (2021). Maternal use of statins in pregnancy: a population-based registry study. Full text in Research Archive
• Christensen, Jacob Juel (2021). What clinical dietitians should know about cholesterol – an update. Full text in Research Archive
• Christensen, Jacob Juel; Bogsrud, Martin P.; Holven, Kirsten B.; Retterstøl, Kjetil; Veierød, Marit B. & Nordeng, Hedvig Marie Egeland (2021). Maternal use of statins in pregnancy: a population-based registry study. Full text in Research Archive
• Christensen, Jacob Juel; Telle-Hansen, Vibeke; Ulven, Stine Marie; Kovanen, Petri T.; Jauhiainen, Matti & Öörni, Katariina [Show all 7 contributors for this article] (2021). The homeoviscous adaptation to dietary lipids (HADL) hypothesis is probably incorrect. American Journal of Clinical Nutrition. ISSN 0002-9165. 113(6), p. 1711–1712. doi: 10.1093/ajcn/nqab110. Full text in Research Archive
• Melnes, Torunn; Bogsrud, Martin Prøven; Thorsen, Ida; Fossum, Julie; Christensen, Jacob J. & Narverud, Ingunn [Show all 9 contributors for this article] (2021). Event-free FH patients >65 years of age are characterized by higher concentration of large HDL particles. Full text in Research Archive
• Narverud, Ingunn; Christensen, Jacob Juel; Bakke, Siril Skaret; Ulven, Stine Marie; Rundblad, Amanda & Aukrust, Pål [Show all 12 contributors for this article] (2020). Profiling of immune‐related gene expression in children with familial hypercholesterolaemia. Full text in Research Archive
• Christensen, Jacob Juel; Ulven, Stine Marie; Thoresen, Magne; Westerman, Kenneth; Holven, Kirsten Bjørklund & Andersen, Lene Frost (2020). Associations between dietary patterns and gene expression pattern in PBMCs: a cross-sectional study. Full text in Research Archive
• Christensen, Jacob Juel (2020). Karbohydrater. Lommelegen.no. Full text in Research Archive Show summary

  https://www.lommelegen.no/ern%C3%A6ring/artikkel/karbohydrater/69589878

• Hustad, Kristin Solheim; Rundblad, Amanda; Ottestad, Inger; Christensen, Jacob J.; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2019). Intake of fatty fish and lipoprotein subclass profiling in healthy adults: a cross-sectional analysis. Full text in Research Archive
• Hustad, Kristin Solheim; Rundblad, Amanda; Ottestad, Inger; Christensen, Jacob J.; Holven, Kirsten Bjørklund & Ulven, Stine Marie (2019). Intake of fatty fish and lipoprotein subclass profiling in healthy adults: a cross-sectional analysis. Full text in Research Archive
• Øyri, Linn Kristin Lie; Bogsrud, Martin Prøven; Christensen, Jacob J.; Ulven, Stine Marie; Brantsæter, Anne Lise & Retterstøl, Kjetil [Show all 12 contributors for this article] (2019). Novel and comprehensive metabolite profiling in cord blood reveal sex differences: A sub-study from the Norwegian Mother, Father and Child Cohort study. Full text in Research Archive
• Christensen, Jacob J. (2018). Statistics and bioinformatics for translational sciences. Full text in Research Archive
• Lysne, Vegard; Olsen, Thomas; Christensen, Jacob J. & Arnesen, Erik (2018). Ja, det er et poeng å bytte til lettbrus! Dagbladet. ISSN 0805-3766. Full text in Research Archive
• Larsen, Sunniva Veen; Holven, Kirsten Bjørklund; Flatberg, Arnar; Christensen, Jacob J.; Leder, Lena & Blomhoff, Rune [Show all 11 contributors for this article] (2018). Effects of replacing saturated fatty acids with polyunsaturated fatty acids on gene expression profiles of human peripheral blood mononuclear cells: a double-blind randomised controlled trial. Full text in Research Archive
• Ulven, Stine Marie; Christensen, Jacob J.; Nygård, Ottar; Svardal, Asbjørn M.; Leder, Lena & Ottestad, Inger [Show all 12 contributors for this article] (2018). Using metabolic profiling to explore molecular effects of replacing saturated fat with polyunsaturated fat- a randomized controlled dietary intervention study. Full text in Research Archive
• Ulven, Stine Marie; Christensen, Jacob J.; Nygård, Ottar; Svardal, Asbjørn M.; Leder, Lena & Ottestad, Inger [Show all 12 contributors for this article] (2018). Using metabolic profiling to explore molecular effects of replacing saturated fat with polyunsaturated fat- a randomized controlled dietary intervention study. Full text in Research Archive
• Blomhoff, Rune; Andersen, Rikke; Arnesen, Erik Kristoffer; Christensen, Jacob Juel; Eneroth, Hanna & Erkkola, Maijaliisa [Show all 13 contributors for this article] (2023). Nordic Nutrition Recommendations 2023. Nordisk ministerråd. doi: 10.6027/nord2023-003. Full text in Research Archive

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